ArticleBMC cancer2016
Hypoxia promotes chemoresistance in acute lymphoblastic leukemia cell lines by modulating death signaling pathways.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- Cytokines, Signaling and Epigenetic Mechanisms: Shaping the Acute Lymphoblastic Leukemia Microenvironment.Cells · 2026Review
- A Comparative Study of Bone Marrow and Central Nervous System Microenvironment Models to Improve In Vitro Studies of Acute Lymphoblastic Leukemia.Hematological oncology · 2025Article
- Article
- Glycolysis Modulation by METTL7B Shapes Acute Lymphoblastic Leukemia Cell Proliferation and Chemotherapy Response.Human cell · 2024Article
- Expression of Long Non-Coding RNA H19 in Acute Lymphoblastic Leukemia.Cell journal · 2023Article
- Hypoxic stress and hypoxia-inducible factors in leukemias.Frontiers in oncology · 2022Review
- Characterization of a novel glucocorticoid-resistant human B-cell acute lymphoblastic leukemia cell line, with AMPK, mTOR and fatty acid synthesis pathway inhibition.Cancer cell international · 2021Article
- Hypoxia and its therapeutic possibilities in paediatric cancers.British journal of cancer · 2021Review
- Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol.Frontiers in oncology · 2021Review
- Overcoming Hypoxia-Induced Chemoresistance in Cancer Using a Novel Glycoconjugate of Methotrexate.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Hypoxia in bone metastasis and osteolysis.Cancer letters · 2020Review
- Inhibition of Oxidative Phosphorylation Reverses Bone Marrow Hypoxia Visualized in Imageable Syngeneic B-ALL Mouse Model.Frontiers in oncology · 2020Article
- Toward Therapeutic Targeting of Bone Marrow Leukemic Niche Protective Signals in B-Cell Acute Lymphoblastic Leukemia.Frontiers in oncology · 2020Review
- Bone marrow microenvironment: The guardian of leukemia stem cells.World journal of stem cells · 2019Review
- A novel method to establish glucocorticoid resistant acute lymphoblastic leukemia cell lines.Journal of experimental & clinical cancer research : CR · 2019Article
- 'Acute leukemia in congenital methehemoglobinemia - an enigma to explore'.Journal of community hospital internal medicine perspectives · 2019Article
- A HIF-independent, CD133-mediated mechanism of cisplatin resistance in glioblastoma cells.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- Chemoresistance Evolution in Triple-Negative Breast Cancer Delineated by Single-Cell Sequencing.Cell · 2018Article
- Integration of hypoxic HIF-α signaling in blood cancers.Oncogene · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeveral studies show that bone marrow (BM) microenvironment and hypoxia condition can promote the survival of leukemic cells and induce resistance to anti-leukemic drugs. However, the molecular mechanism for chemoresistance by hypoxia is not fully understood.
methodsIn the present study, we investigated the effect of hypoxia on resistance to two therapies, methotrexate (MTX) and prednisolone (PRD), in two cell models for acute lymphoblastic leukemia (ALL). To look for an implication of hypoxia in chemoresistance, cell viability, total cell density and cell proliferation were analyzed. Survival and death signaling pathways were also screened by "reverse phase protein array" (RPPA) and western blotting experiments conducted on selected proteins to confirm the results.
resultsWe found that hypoxia promotes chemoresistance in both ALL cell lines. The induction of drug-resistance by hypoxia was not associated with an increase in total cell density nor an increase in cell proliferation. Using RPPA, we show that chemoresistance induced by hypoxia was mediated through an alteration of cell death signaling pathways. This protective effect of hypoxia seems to occur via a decrease in pro-apoptotic proteins and an increase in anti-apoptotic proteins. The results were confirmed by immunoblotting. Indeed, hypoxia is able to modulate the expression of anti-apoptotic proteins independently of chemotherapy while a pro-apoptotic signal induced by a chemotherapy is not modulated by hypoxia.
conclusionsHypoxia is a factor in leukemia cell resistance and for two conventional chemotherapies modulates cell death signaling pathways without affecting total cell density or cell proliferation.
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